Differential Burden of HIV Among Adolescent Girls and Young Women by Places Associated With Sex Work: An Observational Study in Mombasa, Kenya.

BACKGROUND: The design of HIV prevention programs for adolescent girls and young women (AGYW) are informed by data on who is at highest risk and where they can be reached. Places (hotspots) associated with selling sex are an established outreach strategy for sex work (SW) programs but could be used to reach other AGYW at high risk. SETTING: This study took place in Mombasa, Kenya. METHODS: We conducted a cross-sectional, bio-behavioural survey among (N = 1193) sexually active AGYW aged 14-24 years recruited at hotspots. We compared HIV prevalence by subgroup (SW; transactional sex, TS; and non-transactional sex), stratified by hotspot type (venues and nonvenues). We examined whether associations between HIV prevalence and hotspot/subgroup remained after adjustment for individual-level risk factors, and estimated HIV prevalence ratio with and without adjustment for these individual-level factors. RESULTS: Overall HIV prevalence was 5.6%, 5.3% in venues and 7.3% in nonvenues. Overall SW HIV prevalence was 2-fold higher than among participants engaged in nontransactional sex. After adjusting for age and individual-level risk factors, HIV prevalence was 2.72 times higher among venue-based SWs (95% confidence interval: 1.56 to 4.85) and 2.11 times higher among nonvenue AGYW not engaged in SW (95% confidence interval: 0.97 to 4.30) compared with venue-based AGYW not engaged in SW. CONCLUSION: AGYW who sell sex remain at high risk of HIV across types of hotspots. The residual pattern of elevated HIV burden by AGWY subgroup and hotspot type suggests that unmeasured, network-level factors underscore differential risks. As such, hotspots constitute a "place" to reach AGYW at high risk of HIV.

HIV acquisition prior to entry into formal sex work: inference from next-generation viral sequencing.

OBJECTIVE: To infer the timing of HIV acquisition in relation to self-reported events in the sexual life course of adolescent girls and young women (AGYW) who self-identify as female sex workers (FSW) in Mombasa, Kenya. DESIGN: Next-generation viral sequencing of samples of AGYW living with HIV in the Transitions study, a cross-sectional bio-behavioural survey of AGYW aged 14-24 years in Mombasa, Kenya. METHOD: Dried blood spot specimens were collected from study participants ( n  = 37, all FSW). A portion of the HIV pol gene was sequenced using an in-house next-generation sequencing assay for HIV drug resistance mutation genotyping. Estimated time since infection (ETI) was inferred using the HIV EVO web-based tool ( https://hiv.biozentrum.unibas.ch/ETI/ ), and data on self-reported events were obtained from the survey. RESULTS: The median ETI among FSW was 3.4 (interquartile range = 1.7, 6.3) years, with a median ETI of 1.5 years prior to entry into formal sex work. We estimated that 74.1% (95% confidence interval = 53.7-88.9%) of participants living with HIV and who self-identified as FSW likely acquired HIV prior to self-identification as a sex worker. CONCLUSIONS: Findings suggest a large fraction of prevalent HIV infection among AGYW engaged in sex work stems from acquisition prior to entry into formal sex work. Current HIV prevention programs tailored for sex workers may miss key opportunities for HIV prevention as they are designed to reach women after entry into formal sex work, signaling a need for tailored programs to reach high-risk AGYW earlier on in their sexual life course.

Prevalence and patterns of gender-based violence across adolescent girls and young women in Mombasa, Kenya.

BACKGROUND: We sought to estimate the prevalence and describe heterogeneity in experiences of gender-based violence (GBV) across subgroups of adolescent girls and young women (AGYW). METHODS: We used data from a cross-sectional bio-behavioural survey among 1299 AGYW aged 14-24 in Mombasa, Kenya in 2015. Respondents were recruited from hotspots associated with sex work, and self-selected into one of three subgroups: young women engaged in casual sex (YCS), young women engaged in transactional sex (YTS), and young women engaged in sex work (YSW). We compared overall and across subgroups: prevalence of lifetime and recent (within previous year) self-reported experience of physical, sexual, and police violence; patterns and perpetrators of first and most recent episode of physical and sexual violence; and factors associated with physical and sexual violence. RESULTS: The prevalences of lifetime and recent physical violence were 18.0 and 10.7% respectively. Lifetime and recent sexual violence respectively were reported by 20.5 and 9.8% of respondents. Prevalence of lifetime and recent experience of police violence were 34.7 and 25.8% respectively. All forms of violence were most frequently reported by YSW, followed by YTS and then YCS. 62%/81% of respondents reported having sex during the first episode of physical/sexual violence, and 48%/62% of those sex acts at first episode of physical/sexual violence were condomless. In the most recent episode of violence when sex took place levels of condom use remained low at 53-61%. The main perpetrators of violence were intimate partners for YCS, and both intimate partners and regular non-client partners for YTS. For YSW, first-time and regular paying clients were the main perpetrators of physical and sexual violence. Alcohol use, ever being pregnant and regular source of income were associated with physical and sexual violence though it differed by subgroup and type of violence. CONCLUSIONS: AGYW in these settings experience high vulnerability to physical, sexual and police violence. However, AGYW are not a homogeneous group, and there are heterogeneities in prevalence and predictors of violence between subgroups of AGYW that need to be understood to design effective programmes to address violence.

Sexual and reproductive health among adolescent girls and young women in Mombasa, Kenya.

This secondary data analysis of a cross-sectional survey conducted in Mombasa, Kenya characterises sexual and reproductive health (SRH) indicators among adolescent girls and young women (AGYW) engaged in casual and transactional sexual relationships as well as sex work. It describes the association between awareness of local HIV programmes and SRH services uptake for AGYW engaged in sex work. Thirty-eight percent of the participants reported a history of pregnancy. Among participants not trying to get pregnant, 27% stated that they were not currently using any form of contraception. Of the participants who had an abortion, 59% were completed under unsafe conditions. For AGYW engaged in sex work, awareness of local HIV prevention programmes was associated with increased STI testing within the last year (29%) as well as at least one HIV test (99%) compared to those who were not aware of local programming (18% and 92%, respectively); however, only 26% of participants engaged in sex work had heard of local HIV prevention programmes. There were no associations between awareness of local HIV programming and rates of dual contraception use, safe abortion, most recent birth attended by a skilled health professional or testing for HIV during pregnancy. Our study found high need for SRH services, particularly, access to contraception and safe abortion. Continued efforts are required to improve access to the full spectrum of SRH interventions, including family planning services and access to safe abortion in addition to HIV prevention to promote health equity.

Cohort profile: the LHIV-Manitoba clinical cohort of people living with HIV in Manitoba, Canada.

PURPOSE: The LHIV-Manitoba cohort was developed as a way to provide a comprehensive source of HIV-related health information in the central Canadian Prairie province of Manitoba. The cohort will provide important information as we aim to better understand local HIV epidemiology and address key knowledge and practice gaps in HIV prevention, treatment and care programming in the province. PARTICIPANTS: In total, 890 individuals, aged 18 or older and living or receiving HIV care in Manitoba are enrolled in the cohort. A complete clinical dataset exists for 725 participants, which includes variables on sociodemographic characteristics, comorbidities and co-infections, self-reported HIV exposure categories and HIV clinical indicators. A limited clinical dataset exists for an additional 165 individuals who were enrolled posthumously. 97.5% of cohort participants' clinical records are linked to provincial administrative health datasets. FINDINGS TO DATE: The average age of cohort participants is 49.7 years. Approximately three-quarters of participants are male, 42% self-identified as white and 42% as Indigenous. The majority of participants (64%) reported condomless vaginal sex as a risk exposure for HIV. Nearly one-fifth (18%) of participants have an active hepatitis C virus infection and the cohort's median CD4 count increased from 316 cells/mm3 to 518 cells/mm3 between time of entry into care and end of the first quarter in 2019. FUTURE PLANS: The LHIV-Manitoba cohort is an open cohort, and as such, participant enrolment, data collection and analyses will be continually ongoing. Future analyses will focus on the impact of provincial drug plans on clinical outcomes, determinants of mortality among cohort participants and deriving estimates for a local HIV care cascade.

Sex Work Is Associated With Increased Vaginal Microbiome Diversity in Young Women From Mombasa, Kenya.

BACKGROUND: Although nonoptimal vaginal bacteria and inflammation have been associated with increased HIV risk, the upstream drivers of these phenotypes are poorly defined in young African women. SETTING: Mombasa, Kenya. METHODS: We characterized vaginal microbiome and cytokine profiles of sexually active young women aged 14-24 years (n = 168) in 3 study groups: those engaging in formal sex work, in transactional sex, and nonsex workers. Vaginal secretions were collected using self-inserted SoftCup, and assayed for cytokines and vaginal microbiome through multiplex ELISA and 16S rRNA sequencing, respectively. Epidemiological data were captured using a validated questionnaire. RESULTS: The median age of participants was 20 years (interquartile range: 18-22 years). Approximately two-thirds of young women (105/168) had vaginal microbial communities characterized by Gardnerella and/or Prevotella spp. dominance; a further 29% (49/168) were predominantly Lactobacillus iners. Microbiome clustering explained a large proportion of cytokine variation (>50% by the first 2 principal components). Age was not associated with vaginal microbial profiles in bivariable or multivariable analyses. Women self-identifying as sex workers had increased alpha (intraindividual) diversity, independent of age, recent sexual activity, HIV, and other sexually transmitted infections (beta = 0.47, 95% confidence interval: 0.05 to 0.90, P = 0.03). Recent sex (number of partners or sex acts last week, time since last vaginal sex) correlated with increased alpha diversity, particularly in participants who were not involved in sex work. CONCLUSION: Nonoptimal vaginal microbiomes were common in young Kenyan women and associated with sex work and recent sexual activity, but independent of age. Restoring optimal vaginal microflora may represent a useful HIV prevention strategy.

Transitions: Novel Study Methods to Understand Early HIV Risk Among Adolescent Girls and Young Women in Mombasa, Kenya, and Dnipro, Ukraine.

Transitions aims to understand the human immunodeficiency virus (HIV) risk at critical transition points in the sexual life course of adolescent girls and young women (AGYW) who engage in casual sex, transactional sex, and sex work. In this article, we present the Transitions study methods. The Transitions study has the following objectives: (1) to describe how the characteristics and length of the transition period and access gap vary across two epidemiological contexts (Mombasa, Kenya, and Dnipro, Ukraine); (2) to understand how the risk of HIV varies by length and characteristics of the transition period and access gap across epidemiologic contexts; and (3) to assess the extent to which HIV infections acquired during the transition period and access gap could mitigate the population-level impact of focused interventions for female sex workers and explore the potential marginal benefit of expanding programs to reach AGYW during the transition period and access gap. Cross-sectional biobehavioral data were collected from young women aged 14 to 24 years who were recruited from locations in Mombasa County, Kenya, and Dnipro, Ukraine, where sex work took place. Data are available for 1,299 Kenyan and 1,818 Ukrainian participants. The survey addressed the following areas: timing of transition events (first sex, first exchange of sex for money or other resources, self-identification as sex workers, entry into formal sex work, access to prevention program services); sexual behaviors (condom use, anal sex, sex under the influence of drugs or alcohol); partnerships (regular and first-time clients, regular and first-time transactional sex partners, and husbands and boyfriends); alcohol use; injection and non-injection illicit drug use; experience of violence; access to HIV prevention and treatment program; testing for sexually transmitted and blood-borne infections and HIV; and reproductive health (pregnancies, abortions, contraceptives). HIV and hepatitis C virus prevalence data were based on rapid test results. Mathematical modeling will be used to generate projections of onward HIV transmission at specific transition points in the sexual life course of AGYW. Taken together, these data form a novel data resource providing comprehensive behavioral, structural, and biological data on a high-risk group of AGYW in two distinct sociocultural and epidemiologic contexts.

Assessing the influence of conflict on the dynamics of sex work and the HIV and HCV epidemics in Ukraine: protocol for an observational, ethnographic, and mathematical modeling study.

BACKGROUND: Armed conflict erupted in eastern Ukraine in 2014 and still continues. This conflict has resulted in an intensification of poverty, displacement and migration, and has weakened the local health system. Ukraine has some of the highest rates of HIV and Hepatitis C (HCV) in Europe. Whether and how the current conflict, and its consequences, will lead to changes in the HIV and HCV epidemic in Ukraine is unclear. Our study aims to characterize how the armed conflict in eastern Ukraine and its consequences influence the pattern, practice, and experience of sex work and how this affects HIV and HCV rates among female sex workers (FSWs) and their clients. METHODS: We are implementing a 5-year mixed methods study in Dnipro, eastern Ukraine. Serial mapping and size estimation of FSWs and clients will be conducted followed by bio-behavioral cross-sectional surveys among FSWs and their clients. The qualitative component of the study will include in-depth interviews with FSWs and other key stakeholders and participant diaries will be implemented with FSWs. We will also conduct an archival review over the course of the project. Finally, we will use these data to develop and structure a mathematical model with which to estimate the potential influence of changes due to conflict on the trajectory of HIV and HCV epidemics among FSW and clients. DISCUSSION: The limited data that exists on the effect of conflict on disease transmission provides mixed results. Our study will provide rigorous, timely and context-specific data on HIV and HCV transmission in the setting of conflict. This information can be used to inform the design and delivery of HIV and HCV prevention and care services.

Informing HIV Prevention Programs for Adolescent Girls and Young Women: A Modified Approach to Programmatic Mapping and Key Population Size Estimation.

BACKGROUND: Standard programmatic mapping involves identifying locations where key populations meet, profiling of these locations (hotspots), and estimating the key population size. Information gained from this method has been used for HIV programming-resource allocation, program planning, service delivery, and monitoring and evaluation-for people who inject drugs, men who have sex with men, and female sex workers (FSWs). With an increasing focus on adolescent girls and young women (AGYW) as a priority population for HIV prevention, programs need to know the location of and how to effectively reach individuals who are at increased risk for HIV but were conventionally considered part of the general population. We hypothesize that AGYW who engage in transactional and casual sex also congregate at sex work hotspots to meet sex partners. Therefore, we adapted the standard programmatic mapping approach to understand the geographic distribution and population size of AGYW at increased HIV risk in Mombasa County, Kenya. OBJECTIVES: The objectives are several-fold: (1) detail and compare the modified programmatic mapping approach used in this study to the standard approach, (2) estimate the number of young FSWs, (3) estimate the number of AGYW who congregate in sex work hotspots to meet sex partners other than clients, (4) estimate the overlap in sexual network in hotspots, (5) describe the distribution of sex work hotspots across Mombasa and its four subcounties, and (6) compare the distribution of hotspots that were known to the local HIV prevention program prior to this study and those newly identified. METHODS: The standard programmatic mapping approach was modified to estimate the population of young women aged 14 to 24 years who visit sex work hotspots in Mombasa to meet partners for commercial, transactional, and casual sex. RESULTS: We estimated that there were 11,777 FSWs (range 9265 to 14,290) in Mombasa in 2014 among whom 6127 (52.02%) were 14 to 24 years old. The population estimates for women aged 14 to 24 years who engaged in transactional and casual sex and congregated at the hotspots were 5348 (range 4185 to 6510) and 4160 (range 3194 to 5125), respectively. Of the 1025 validated sex work hotspots, 870 (84.88%) were locations also visited by women engaged in transactional and casual sex. Only 47 (4.58%) hotspots were exclusive sex work locations. The geographic and typological distribution of hotspots were significantly different between the four subcounties (P<.001). Of the 1025 hotspots, 419 (40.88%) were already known to the local HIV prevention program and 606 (59.12%) were newly identified. CONCLUSIONS: Using the adapted programmatic mapping approach detailed in this study, our results show that HIV prevention programs tailored to AGYW can focus delivery of their interventions to sex work hotspots to reach subgroups that may be at increased risk for HIV.

Vulnerabilities at First Sex and Their Association With Lifetime Gender-Based Violence and HIV Prevalence Among Adolescent Girls and Young Women Engaged in Sex Work, Transactional Sex, and Casual Sex in Kenya.

BACKGROUND: Adolescent girls and young women (AGYW) experience high rates of HIV early in their sexual life course. We estimated the prevalence of HIV-associated vulnerabilities at first sex, and their association with lifetime gender-based violence (GBV) and HIV. METHODS: We conducted a cross-sectional biobehavioral survey among AGYW (14-24 years) in Mombasa, Kenya in 2015. We compared the prevalence of first sex vulnerabilities across AGYW who self-identified as engaging in sex work (N = 408), transactional sex (N = 177), or casual sex (N = 714) and used logistic regression to identify age-adjusted associations between first sex vulnerabilities and outcomes (GBV after first sex; HIV). RESULTS: The median age at first sex was 16 years (interquartile range 14-18). A total of 43.6% received gifts or money at first sex; 41.2% and 11.2% experienced a coerced and forced first sex, respectively. First sex vulnerabilities were generally more common among AGYW in sex work. GBV (prevalence 23.8%) and HIV (prevalence 5.6%) were associated with first sex before age 15 [GBV adjusted odds ratio (AOR) 1.4, 95% confidence interval (CI): 1.0 to 1.9; HIV AOR 1.9, 95% CI: 1.1 to 1.3]; before or within 1 year of menarche (GBV AOR 1.3, 95% CI: 1.0 to 1.7; HIV AOR 2.1, 95% CI: 1.3 to 3.6); and receipt of money (GBV AOR 1.9, 95% CI: 1.4 to 2.5; HIV AOR 2.0, 95% CI: 1.2 to 3.4). CONCLUSIONS: HIV-associated vulnerabilities begin at first sex and potentially mediate an AGYW's trajectory of risk. HIV prevention programs should include structural interventions that reach AGYW early, and screening for a history of first sex vulnerabilities could help identify AGYW at risk of ongoing GBV and HIV.

The contributions and future direction of Program Science in HIV/STI prevention.

BACKGROUND: Program Science is an iterative, multi-phase research and program framework where programs drive the scientific inquiry, and both program and science are aligned towards a collective goal of improving population health. DISCUSSION: To achieve this, Program Science involves the systematic application of theoretical and empirical knowledge to optimize the scale, quality and impact of public health programs. Program Science tools and approaches developed for strategic planning, program implementation, and program management and evaluation have been incorporated into HIV and sexually transmitted infection prevention programs in Kenya, Nigeria, India, and the United States. CONCLUSION: In this paper, we highlight key scientific contributions that emerged from the growing application of Program Science in the field of HIV and STI prevention, and conclude by proposing future directions for Program Science.

Strong memory CD8+ T cell responses against immunodominant and three new subdominant HLA-B27-restricted influenza A CTL epitopes following secondary infection of HLA-B27 transgenic mice.

We previously showed that the known HLA-B27-restricted influenza A epitope identified from human studies, NP.383-391, was recognized by CTLs following influenza A infection of transgenic (Tg) HLA-B27/H2 class I-deficient (H2 DKO) mice. Here, we examined the kinetics of the primary NP.383-391-specific response in Tg HLA-B27/H2 DKO mice at the site of respiratory infection, along with the profile of additional influenza A epitopes recognized. While the temporal kinetics of the Tg HLA-B27/NP.383-391-specific CD8+ T cell response paralleled the H2-D(b)/NP.366-374-specific response of non-Tg H2b mice, the magnitude was less. Using epitope prediction programs, we identified three novel B27-restricted influenza A epitopes, PB2.702-710, PB1.571-579, and PB2.368-376, recognized during both the primary and secondary response to infection. Although the secondary NP.383-391-specific response was dominant, PB1.571-579 and PB2.368-376 stimulated stronger proliferative expansion in memory T cells. Our results indicate a broader B27/influenza A CTL repertoire than previously known. Together with results for other HLA class I alleles, this information will become important in improving vaccine strategies for influenza A and other human pathogens.

Highly conserved pattern of recognition of influenza A wild-type and variant CD8+ CTL epitopes in HLA-A2+ humans and transgenic HLA-A2+/H2 class I-deficient mice.

As an in vivo model for studying human MHC (HLA) class I-restricted CTL responses to viral infection, we established a series of HLA Tg mice expressing HLA-A2, -B7 or -B27 human/mouse hybrid genes on a background deficient for H2 class I (Tg HLA(hyb)/H2 class I DKO). To determine whether CTL recognition of influenza A (flu) infection in Tg HLA-A2(hyb)/H2 DKO mice is similar to HLA-A2+ humans, we compared the HLA-A2-restricted Tg mouse and human CD8+ T-cell responses to an immunodominant flu epitope (wild-type [WT] M1 58-66), as well as a variant of this peptide (var. M1 58-66). Similar to HLA-A2+ humans, our results show WT M1 58-66 is likely the dominant CTL epitope recognized in infected Tg HLA-A2(hyb)/H2 DKO mice. Var. M1 58-66 was also recognized by WT peptide-reactive T cells from both HLA-A2+ humans and Tg mice, although slightly less efficiently than WT M1 58-66 in both cases. Reduced variant recognition was shown to be associated with reduced peptide/A2 binding, as well as a more limited repertoire of utilized TCR Vbeta chains. The similar pattern of recognition and cross reaction observed here for the WT and variant M1 58-66 epitopes with HLA-A2 by human and Tg HLA mouse CTLs indicates that A2-dependent events of Ag processing, presentation and recognition are well-conserved between species. These findings demonstrate that this Tg HLA-A2/H2 DKO model will aid identification and development of epitopes as vaccines for numerous viral and tumor antigens for the HLA-A2 supertype.

Human MHC class I transgenic mice deficient for H2 class I expression facilitate identification and characterization of new HLA class I-restricted viral T cell epitopes.

Although mice transgenic (Tg) for human MHC (HLA) class I alleles could provide an important model for characterizing HLA-restricted viral and tumor Ag CTL epitopes, the extent to which Tg mouse T cells become HLA restricted in the presence of endogenous H2 class I and recognize the same peptides as in HLA allele-matched humans is not clear. We previously described Tg mice carrying the HLA-B27, HLA-B7, or HLA-A2 alleles expressed as fully native (HLA(nat)) (with human beta(2)-microglobulin) and as hybrid human/mouse (HLA(hyb)) molecules on the H2(b) background. To eliminate the influence of H2(b) class I, each HLA Tg strain was bred with a H2-K(b)/H2-D(b)-double knockout (DKO) strain to generate mice in which the only classical class I expression was the human molecule. Expression of each HLA(hyb) molecule and HLA-B27(nat)/human beta(2)-microglobulin led to peripheral CD8(+) T cell levels comparable with that for mice expressing a single H2-K(b) or H2-D(b) gene. Influenza A infection of Tg HLA-B27(hyb)/DKO generated a strong CD8(+) T cell response directed at the same peptide (flu nucleoprotein NP383-391) recognized by CTLs from flu-infected B27(+) humans. As HLA-B7/flu epitopes were not known from human studies, we used flu-infected Tg HLA-B7(hyb)/DKO mice to examine the CTL response to candidate peptides identified based on the B7 binding motif. We have identified flu NP418-426 as a major HLA-B7-restricted flu CTL epitope. In summary, the HLA class I Tg/H2-K/H2-D DKO mouse model described in this study provides a sensitive and specific approach for identifying and characterizing HLA-restricted CTL epitopes for a variety of human disease-associated Ags.